Endoscopy 2004; 36(2): 170-173
DOI: 10.1055/s-2004-814185
Original Article
© Georg Thieme Verlag Stuttgart · New York

Botulinum Toxin Injection after Biliary Sphincterotomy

A.  Gorelick1 , J.  Barnett2 , W.  Chey2 , M.  Anderson2 , G.  Elta2
  • 1Connecticut Gastroenterology Consultants, P.C., New Haven, Connecticut, USA
  • 2University of Michigan Medical Center, Ann Arbor, Michigan, USA
Further Information

Publication History

Submitted 28 January 2002

Accepted after Revision 9 July 2003

Publication Date:
06 February 2004 (online)

Background and Study Aims: Endoscopic biliary sphincterotomy in patients with sphincter of Oddi dysfunction (SOD) is associated with a high risk of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP), which may be secondary to residual pancreatic sphincter hypertension. It was hypothesized that botulinum toxin injection could be used to reduce pancreatic sphincter hypertension temporarily in SOD patients after biliary sphincterotomy, thereby reducing the rate of procedure-induced pancreatitis.
Patients and Methods: All patients undergoing ERCP with manometry due to a suspected biliary SOD were asked to participate in the study. Patients with elevated basal sphincter pressures were randomly assigned to receive either botulinum toxin or a sham saline injection after biliary sphincterotomy. Fifty units of botulinum toxin were delivered via a sclerotherapy needle in the form of two 25-U injections of 0.25 ml each into the pancreatic sphincter. In patients in the sham arm, 0.50 ml of saline was injected into the duodenal lumen.

Results: Between 12 February 1999 and 29 November 2000, a total of 98 patients were referred for ERCP with manometry; 86 consented to participate in the study, and 26 had elevated baseline pressures and underwent random assignment. Twelve received botulinum toxin injection and 14 were randomly assigned to receive the sham injection. A total of six patients in the sham group (43 %) developed procedure-induced pancreatitis, compared with three patients in the botulinum toxin group (25 %; P = 0.34).
Conclusions: Biliary sphincterotomy in patients with sphincter of Oddi dysfunction without pancreatic protection is risky and should no longer be carried out. This study demonstrates that botulinum toxin injection into the residual pancreatic sphincter after biliary sphincterotomy is technically feasible and safe, showing a trend toward a reduced post-ERCP pancreatitis rate in patients with sphincter of Oddi dysfunction. Further studies will need to confirm the validity of these experimental results before this technique can be used routinely.

References

  • 1 Cotton P B, Lehman G, Vennes J. et al . Endoscopic sphincterotomy complications and their management: an attempt at consensus.  Gastrointest Endosc. 1991;  37 383-393
  • 2 Sherman S, Lehman G A. ERCP- and endoscopic sphincterotomy-induced pancreatitis.  Pancreas. 1991;  6 350-367
  • 3 Freeman M L, Nelson D B, Sherman S. et al . Complications of endoscopic biliary sphincterotomy.  N Engl J Med. 1996;  335 909-918
  • 4 Bozkurt T, Orth K, Butsch B. et al . Long-term clinical outcome of post-cholecystectomy patients with biliary-type pain: results of manometry, non-invasive techniques and endoscopic sphincterotomy.  Eur J Gastroenterol Hepatol. 1996;  8 245-249
  • 5 Wehrmann T, Wiemer K, Lembcke B. et al . Do patients with sphincter of Oddi dysfunction benefit from endoscopic sphincterotomy? A 5-year prospective trial.  Eur J Gastroenterol Hepatol. 1996;  8 251-256
  • 6 Botoman V A, Kozarek R A, Novell L A. et al . Long-term outcome after endoscopic sphincterotomy in patients with biliary colic and suspected sphincter of Oddi dysfunction.  Gastrointest Endosc. 1994;  40 165-170
  • 7 Sherman S, Hawes R H, Rathgaber S W. et al . Post-ERCP pancreatitis: randomized, prospective study comparing a low- and high-osmolality contrast agent.  Gastrointest Endosc. 1994;  40 422-427
  • 8 Choudhry U, Ruffolo T, Jamidar P. et al . Sphincter of Oddi dysfunction in patients with intact gallbladder: therapeutic response to endoscopic sphincterotomy.  Gastrointest Endosc. 1993;  39 492-495
  • 9 Sherman S, Ruffolo T A, Hawes R H. et al . Complications of endoscopic sphincterotomy: a prospective series with emphasis on the increased risk associated with sphincter of Oddi dysfunction and nondilated ducts.  Gastroenterology. 1991;  101 1068-1075
  • 10 Chen Y K, Foliente R L, Santoro M J. et al . Endoscopic sphincterotomy-induced pancreatitis: increased risk associated with nondilated bile ducts and sphincter of Oddi dysfunction.  Am J Gastroenterol. 1994;  89 327-333
  • 11 Tarnasky P, Cunningham J, Cotton P. et al . Pancreatic sphincter hypertension increases the risk of post-ERCP pancreatitis.  Endoscopy. 1997;  29 252-257
  • 12 Simpson L L. The origin, structure, and pharmacological activity of botulinum toxin.  Pharmacol Rev. 1981;  33 155-188
  • 13 Pasricha P J, Ravich W J, Hendrix T R. et al . Intrasphincteric botulinum toxin for the treatment of achalasia.  N Engl J Med. 1995;  332 774-778
  • 14 Hallan R I, Williams N S, Melling J. et al . Treatment of anismus in intractable constipation with botulinum A toxin.  Lancet. 1988;  ii 714-717
  • 15 Gui D, Cassetta E, Anastasio G. et al . Botulinum toxin for chronic anal fissure.  Lancet. 1994;  344 1127-1128
  • 16 Zhao X, Pasricha P J. Botulinum toxin for spastic GI disorders: a systematic review.  Gastrointest Endosc. 2003;  57 219-235
  • 17 Okolo P I, Wadwa K, Magee C A. et al . Immediate reduction of pancreatic SO pressure after endoscopic injection of botulinum toxin (BoTox): implications for prevention of ERCP-induced pancreatitis [abstract].  Gastroenterology. 1998;  114 A535
  • 18 Muehldorfer S M, Hahn E G, Ell C. Botulinum toxin as a diagnostic tool of verification of sphincter of Oddi dysfunction causing recurrent pancreatitis.  Endoscopy. 1997;  29 120-124
  • 19 Di Francesco V, Bertolasi L, Angelini G. et al . Injection of botulinum toxin into the sphincter of Oddi in patients with acute recurrent pancreatitis: an effective ”medical sphincterotomy” [abstract].  Gastroenterology. 1998;  114 A453
  • 20 Toouli J, Roberts-Thomson I C, Dent J, Lee J. Manometric disorders in patients with suspected sphincter of Oddi dysfunction.  Gastroenterology. 1985;  88 1243-1250
  • 21 Sherman S, Troiano F P, Hawes R H. et al . Sphincter of Oddi manometry: decreased risk of clinical pancreatitis with use of a modified aspirating catheter.  Gastrointest Endosc. 1990;  36 462-466
  • 22 Tarnasky P R, Palesch Y, Cunningham J T. et al . Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction: a prospective randomized trial [abstract].  Gastrointest Endosc. 1997;  45 AB150
  • 23 Eversman D, Fogel E, Gottlieb K. et al . Sphincter of Oddi dysfunction (SOD): combined pancreatobiliary therapy (PBRx) has a lower post-procedure pancreatitis rate than pull-type biliary sphincterotomy (BES) [abstract].  Gastrointest Endosc. 1998;  47 AB113
  • 24 Meshkinpour H, Kay L, Mollot M. The role of the flow rate of the pneumohydraulic system on post-sphincter of Oddi manometry pancreatitis.  J Clin Gastroenterol. 1992;  14 236-239
  • 25 Johnson G K, Geenen J E, Bedford R A. et al . A comparison of nonionic versus ionic contrast media: results of a prospective, multicenter study.  Gastrointest Endosc. 1995;  42 312-316
  • 26 Smithline A, Silverman W, Rogers D. et al . Effect of prophylactic main pancreatic duct stenting on the incidence of biliary endoscopic sphincterotomy-induced pancreatitis in high-risk patients.  Gastrointest Endosc. 1993;  39 652-657
  • 27 Silverman W B, Ruffolo T A, Sherman S. et al . Correlation of basal sphincter pressures measured from the bile duct and the pancreatic duct in patients with suspected sphincter of Oddi dysfunction.  Gastrointest Endosc. 1992;  38 440-443
  • 28 Rolny P, Arleback A, Funch-Jensen P. et al . Clinical significance of manometric assessment of both pancreatic duct and bile duct sphincter in the same patients.  Scand J Gastroenterol. 1989;  24 751-754
  • 29 Eversman D, Sherman S, Bucksot L. et al . Frequency of abnormal biliary and pancreatic basal sphincter pressure at sphincter of Oddi manometry in 463 patients [abstract].  Gastrointest Endosc. 1996;  43 381
  • 30 Knapple W, Tarnasky P, Coyle W. et al . Sphincter of Oddi manometry of both ducts after conscious sedation with meperidine [abstract].  Gastrointest Endosc. 1996;  43 385
  • 31 Tarnasky P R, Cunningham J T, Knapple W L. et al . Repeat pancreatic sphincter manometry after biliary sphincterotomy in patients with sphincter of Oddi dysfunction [abstract].  Gastrointest Endosc. 1997;  45 AB151
  • 32 Tarnasky P R, Palesch Y Y, Cunningham J T. et al . Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction.  Gastroenterology. 1998;  115 1518-1524
  • 33 Pasricha P J, Miskovsky E P, Kalloo A N. Intrasphincteric injection of botulinum toxin for suspected sphincter of Oddi dysfunction.  Gut. 1994;  35 1319-1321
  • 34 Wang H J, Tanaka M, Konomi H. et al . Effect of local injection of botulinum toxin on sphincter of Oddi cyclic motility in dogs.  Dig Dis Sci. 1998;  43 694-701
  • 35 Sand J, Nordback I, Arvola P. et al . Effects of botulinum toxin A on the sphincter of Oddi: an in vivo and in vitro study.  Gut. 1998;  42 507-510
  • 36 Pasricha P J, Sostre S, Kalloo A N. Endoscopic injection of botulinum toxin for patients with suspected sphincter of Oddi dysfunction: results of a pilot trial [abstract].  Gastrointest Endosc. 1994;  40 421
  • 37 Wehrmann T, Seifert H, Seipp M. et al . Endoscopic injection of botulinum toxin for biliary sphincter of Oddi dysfunction.  Endoscopy. 1998;  30 702-707
  • 38 Patti M G, Feo C V, Arcerito M. et al . Effects of previous treatment on results of laparoscopic Heller myotomy for achalasia.  Dig Dis Sci. 1999;  44 2270-2276

G. Elta, M. D.

Division of Gastroenterology

3912 Taubman Center · Ann Arbor · MI 48109-0362 · USA ·

Fax: + 1-734-936-7392

Email: gelta@umich.edu

    >